Human Cytochrome P450 2C9 and Its Polymorphic Modifications: Electroanalysis, Catalytic Properties, and Approaches to the Regulation of Enzymatic Activity.

Shumyantseva, Victoria V.; Bulko, Tatiana V.; Koroleva, Polina I.; Shikh, Evgeniya V.; Makhova, Anna A.; Kisel, Maryia S.; Haidukevich, Irina V.; Gilep, Andrei A.

The electrochemical properties of cytochrome P450 2C9 (CYP2C9) and polymorphic modifications P450 2C9*2 (CYP2C9*2) and P450 2C9*3 (CYP2C9*3) were studied. To analyze the comparative electrochemical and electrocatalytic activity, the enzymes were immobilized on electrodes modified with a membrane-like synthetic surfactant (didodecyldimethylammonium bromide (DDAB)). An adequate choice of the type of modified electrode was confirmed by cyclic voltammetry of cytochromes P450 under anaerobic conditions, demonstrating well-defined peaks of reduction and oxidation of the heme iron. The midpoint potential, Emid, of cytochrome P450 2C9 is −0.318 ± 0.01 V, and Emid = −0.324 ± 0.01 V, and Emid = −0.318 ± 0.03 V for allelic variant 2C9*2 and allelic variant 2C9*3, respectively. In the presence of substrate diclofenac under aerobic conditions, cytochrome P450 2C9 and its polymorphic modifications P450 2C9*2 and P450 2C9*3 exhibit catalytic properties. Stimulation of the metabolism of diclofenac by cytochrome P450 2C9 in the presence of antioxidant medications mexidol and taurine was shown.

CYTOCHROME P-450; ELECTROCHEMICAL analysis; IRON oxidation; CYTOCHROMES; CYCLIC voltammetry; CYTOCHROME c

Processes, 2022, Vol 10, Issue 2, p383

2227-9717

Academic Journal

10.3390/pr10020383